Cilansetron acts at its site of absorption to antagonize the sensitivity of mesenteric afferent fibres to 5-hydroxytryptamine in the rat jejunum.

The present study compares the efficacy of cilansetron, a 5-hydroxytryptamine (5-HT3)-receptor antagonist, delivered via intravenous and intraluminal routes, on the sensitivity of mesenteric afferent fibres supplying the proximal jejunum. Waveform analysis was performed to extract 5-HT sensitive single units from electrophysiological recordings of whole afferent nerve discharge. Dose effects of intravenous cilansetron (0.2-20 microg/kg) on the afferent response to 5-HT (10 microg) were examined to determine the threshold dose of cilansetron (2 microg/kg). This dose applied intraluminally to the region of jejunum innervated by the afferents, resulted in a greater degree of antagonism of the 5-HT response than intravenous administration (47.8+/-7.9 vs. 76.9+/-4.7%, P = 0.008). We concluded that cilansetron is active at its site of absorption to antagonize 5-HT3 receptors on vagal mucosal afferent terminals.